Integrin and cadherin synergy regulates contact inhibition of migration and motile activity.
Integrin and cadherin synergy regulates contact inhibition of migration and motile activity.
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DOI：
10.1083/jcb.141.2.515
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发表时间：
1998-04-20
影响因子：
7.8
通讯作者：
Horwitz, AF
中科院分区：
文献类型：
--
作者：
Huttenlocher, A;Lakonishok, M;Kinder, M;Wu, S;Truong, T;Knudsen, KA;Horwitz, AF
整合素受体通过其作为其他细胞和细胞外基质组分的粘附受体的作用在细胞迁移中发挥核心作用。在这项研究中，我们证明，整合素和钙粘蛋白受体协调调节接触介导的抑制细胞迁移。除了促进增殖（Sastry，S.，M. Lakonishok，D.托马斯，J. Muschler和A.霍维茨1996. J. Cell Biol.133：169-184），α5整联蛋白在原代鹌鹑成肌细胞培养物中的异位表达促进了细胞迁移的显著接触介导的抑制。异位表达α5整联蛋白的成肌细胞（α5成肌细胞）在不接触时正常移动，但在接触时，它们显示出迁移和运动活性的抑制（即，膜突起的延伸和收缩）。因此，这些细胞倾向于聚集生长，并且不迁移以闭合伤口。这种表型也见于β1整联蛋白、桩蛋白或活化的FAK（CD 2 FAK）的异位表达，因此似乎是整联蛋白介导的信号传导增强所致。在α5成肌细胞中观察到的接触抑制由N-钙粘蛋白介导，其表达上调超过5倍。扰动研究使用低钙条件下，抗体抑制，和异位表达的野生型和突变型N-钙粘蛋白都牵连N-钙粘蛋白的接触抑制迁移。N-钙粘蛋白的异位表达也产生接触后显示出抑制迁移的细胞;然而，它们没有显示出抑制的运动活性，这表明整合素和钙粘蛋白协同调节运动活性。这些观察结果对胚胎发育过程中的正常和病理过程以及肿瘤转移具有潜在的重要意义。
Integrin receptors play a central role in cell migration through their roles as adhesive receptors for both other cells and extracellular matrix components. In this study, we demonstrate that integrin and cadherin receptors coordinately regulate contact-mediated inhibition of cell migration. In addition to promoting proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz. 1996. J. Cell Biol. 133:169–184), ectopic expression of the α5 integrin in cultures of primary quail myoblasts promotes a striking contact-mediated inhibition of cell migration. Myoblasts ectopically expressing α5 integrin (α5 myoblasts) move normally when not in contact, but upon contact, they show inhibition of migration and motile activity (i.e., extension and retraction of membrane protrusions). As a consequence, these cells tend to grow in aggregates and do not migrate to close a wound. This phenotype is also seen with ectopic expression of β1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore appears to result from enhanced integrin-mediated signaling. The contact inhibition observed in the α5 myoblasts is mediated by N-cadherin, whose expression is upregulated more than fivefold. Perturbation studies using low calcium conditions, antibody inhibition, and ectopic expression of wild-type and mutant N-cadherins all implicate N-cadherin in the contact inhibition of migration. Ectopic expression of N-cadherin also produces cells that show inhibited migration upon contact; however, they do not show suppressed motile activity, suggesting that integrins and cadherins coordinately regulate motile activity. These observations have potential importance to normal and pathologic processes during embryonic development and tumor metastasis.
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影响因子：
15.9
作者：
Caveda, L;MartinPadura, L;Dejana, E
通讯作者：
Dejana, E
影响因子：
2.7
作者：
GeorgeWeinstein, M;Gerhart, J;Knudsen, KA
通讯作者：
Knudsen, KA
影响因子：
3.7
作者：
ABERCROMBIE, M;HEAYSMAN, JEM
通讯作者：
HEAYSMAN, JEM
影响因子：
3.3
作者：
FUJIMORI, T;TAKEICHI, M
通讯作者：
TAKEICHI, M
通过整联蛋白介导的细胞骨架链接和配体结合亲和力调节细胞迁移。
影响因子：
7.8
作者：
Huttenlocher, A;Ginsberg, MH;Horwitz, AF
通讯作者：
Horwitz, AF